Butylated hydroxyanisole (BHA) is a commonly used food-additive antioxidant. When added to the diet, it has been shown to reduce the incidence of chemically induced tumors in animal models. This project proposes to study the mechanisms of the anticarcinogenic action of BHA using several approaches with mice and rats. Previously, we have observed that BHA inhibits the mixed-function oxidase (MFO) system and is more effective towards the aryl hydrocarbon hydroxylase of the lung than that of the liver. This inhibitory action will be substantiated further in reconstituted systems with purified lung and liver MFO enzymes. The effect of BHA on the pattern of benzo[a]pyrene (BP) metabolites produced by microsomes and reconstituted MFO systems will be examined by high pressure liquid chromatography. The effects of dietary BHA on the physical properties and metabolic activities of lung and liver cytochrome P-450 will be studied. The effects of dietary BHA on the metabolism of BP will be investigated by (a) measuring the pattern of urinary excretion of radioactive BP and its metabolites, (b) analyzing the appearance and clearance of BP and its metabolites in the blood, (c) examining the BP and its metabolites in the lung as a function of time, and (d) studying the meabolism of BP in perfused lungs. Through the systematic analysis of these factors, we hope to elucidate the biochemical mechanisms of the anticarcinogenic action of BHA.